The goal of the current study is to determine stability of compounded 5-fluorouracil (5-FU) in Intravia™ bags and CADD™ cassettes stored up to 15 days under refrigeration (2-8°C) and room temperature (25°C with 60% relative humidity), with four different concentrations (20 mg/mL, 30 mg/mL, 40 mg/mL, and 50 mg/mL) and two diluents (0.9% sodium chloride and 5% dextrose). A stability-indicating high-performance liquid chromatography (HPLC) method was developed to analyze the 5-FU concentrations. The stability of compounded 5-FU infusions was investigated using this method. Two samples from each storage condition were assessed for stability on days 0, 4, 7, 10, and 15 as per United States Pharmacopeia (USP) guidelines. The assay of 5-FU was done utilizing a calibrated stability-indicating HPLC method. The stability-indicating HPLC assay showed 5-FU completely degraded within 1 hour in basic conditions. No cloudiness or color change was observed during the stability study. Precipitation was observed in the CADD™ cassettes at day 15 in both storage conditions and at day 10 in a single room-temperature CADD™ cassette for 40 mg/mL in 5% dextrose (D5W). HPLC assay revealed the infusions in CADD™ cassettes retained greater than 90% of the initial concentrations of 5-FU for 15 days stored at room temperature (25°C and 60% relative humidity) and for 10 days at refrigeration (2-8°C). Intravia™ bags retained stability through 15 days for all the compounded 5-FU concentrations and both the storage conditions. 5-FU infusions in both CADD™ cassettes and Intravia™ bags were stable for extendable periods in multiple concentrations compared to recommended guidelines for hospital use.
We aim to evaluate the association between serum 25-hydroxyvitamin D3 levels and total number, volume and location of uterine fibroids (UFs) in premenopausal women in North Indian population. This case control study was undertaken in 310 women between 18 years and 45 years of age. Cases comprised of 102 women with fibroid lesion and the control group included 208 women with normal uterine morphology on ultrasonography. Blood samples were taken for measuring 25-hydroxyvitamin D3 levels. The mean serum 25-hydroxyvitamin D3 level in the study and control group was 14.52 ± 7.89 ng/mL and 26.6 ± 14.36 ng/mL respectively (p < 0.05). There was significant inverse correlation between serum 25-hydroxyvitamin D3 levels and total volume of fibroids (p = 0.000) while none between 25-hydroxyvitamin D3 levels with location, number of fibroids. 25-hydroxyvitamin D3 deficiency was more common in the study group (54.90%) compared to healthy controls (6.7%) while sufficiency was more common among controls (67.8% vs. 27.45) (p < 0.05). Women with deficient 25-hydroxyvitamin D3 levels have an odds of 18.36 for developing uterine fibroid. Women with low parity, those belonging to higher socioeconomic status and having less than 1-hour sun exposure per day were independently found to have high risk for development of UFs. Vitamin D may have a role in growth of UFs. Women not able to get adequate sun exposure due to indoor working conditions may need evaluation and supplementation as prophylaxis for development of fibroid.
Accumulating evidence has been reported regarding the effect of curcumin as a dietary antiviral on patients with COVID-19; however, findings are controversial. Our systematic review aimed to evaluate the effects of curcumin in patients with COVID-19. Electronic databases (PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar) were systematically searched to identify only randomized clinical trials (RCTs) that assessed curcumin in patients with COVID-19 from inception to September 23, 2021 relevant keywords. The Cochrane risk-of-bias tool for randomized trials was used to evaluate the risk of bias. After a critical review of 1,098 search hits, only six RCTs were selected for discussion. A total of 480 patients were included, with 240 amongst the curcumin groups and 240 in the control group. The lymphocyte count was significantly higher in the curcumin group compared to the placebo group. Curcumin was found to decrease the number of T-helper 17 cells, downregulate T-helper-17 cell‐related factors, reduce levels of T-helper-17 cell‐related cytokines, yet increase the gene expression of Treg transcription factor forkhead box P3 (FOXP3), and decrease T-Box transcription factor 21 (TBX21). Our review revealed that curcumin might have a positive effect on relieving COVID-19 related inflammatory response due to its powerful immune‐modulatory effects on cytokines production, T-cell responses, and gene expression. These findings suggest that curcumin confers clinical benefits in patients with COVID-19. However, due to the limited number of the included studies, further high-quality studies are needed to establish the clinical efficacy of the curcumin.
Previous studies have proposed that pelvic misalignment may be associated with stress urinary incontinence through a decrease in the contractile function of the pelvic floor muscles; however, this relationship remains unclear. This study aimed to clarify the relationship between low back pain, an indication of pelvic misalignment, and stress urinary incontinence at 3 months postpartum. We conducted a cross-sectional study of women who gave birth to full-term babies between July 2008 and July 2009. Stress urinary incontinence was defined as urinary leakage when coughing, sneezing, or exercising. Low back pain was defined as pain between the ribs and gluteal sulcus in the preceding 2 months. Of the 228 subjects included in the study, the prevalence of stress urinary incontinence was 22.8% (n = 52). The prevalence of low back pain in the stress urinary incontinence group was significantly higher than that in the non-stress urinary incontinence group (78.8% [n = 41] vs. 57.4% [n = 101]; p = 0.005). Stress urinary incontinence was associated with older age, primiparity, vaginal delivery, and low back pain at 3 months. In conclusion, low back pain was associated with stress urinary incontinence after adjusting for pregnancy and delivery factors, suggesting pelvic misalignment contributes to the development of stress urinary incontinence. We propose that including care for pelvic misalignment in pelvic floor muscle training, the treatment of choice for stress urinary incontinence, could be beneficial.
As of the end of November, 2021, the rate of completion for second-dose COVID-19 vaccine administration was almost 80% in Japan. We evaluated waning COVID-19 vaccine effectiveness in Japan, controlling for mutated strains, the Olympic Games, and countermeasures. The effective reproduction number R(t) was regressed on current vaccine coverage and data of a certain number of days prior, as well as shares of mutated strains, and an Olympic Games dummy variable along with data of temperature, humidity, mobility, and countermeasures. The study period was February, 2020 through November 4, as of November 25, 2021. Estimation results indicate that vaccine coverage of more than 90 days prior raises R(t) significantly. Especially, vaccine coverage with 90 or 120 days prior cancelled vaccine effectiveness completely. Results indicate significant waning of vaccine effectiveness from 90 days after the second dose.
Persistence of urinary incontinence (UI) after robot-assisted radical prostatectomy (RARP) is a bothersome problem because of its negative effect on the patient’s quality of life (QOL). This study aimed to evaluate the effect of transperineal ultrasound (TPUS)-guided pelvic floor muscle training (PFMT) on prolonged UI after RARP. Thirty men with stress UI persisting for > 1 year after RARP underwent biofeedback PFMT using TPUS once every 2-3 weeks for 3 months. The frequency and duration of sustaining pelvic floor muscle (PFM) contractions were assessed using ultrasound imaging. The severity of UI and UI-related QOL were evaluated using a 24-hour pad test and the incontinence quality of life (I-QOL) questionnaire. Twenty-four men (mean age, 72.2 years) completed the TPUS-guided PFMT. The mean duration from RARP to PFMT was 1,228.9 days. The mean cumulative session and the total duration of TPUS-guided PFMT were 4.6 times and 73.3 days, respectively. Compared with the data before TPUS-guided PFMT, the frequency of PFM contractions and duration of sustaining contraction significantly improved after TPUS-guided PFMT (p < 0.05). Additionally, the total amount of urinary leakage after TPUS-guided PFMT was reduced significantly (248.6 ± 280.6 g vs. 397.0 ± 427.0 g, p = 0.024). The I-QOL score was significantly increased after TPUS-guided PFMT (72.1 ± 16.8 vs. 61.0 ± 19.0, p < 0.001). TPUS-guided PFMT may be effective in improving prolonged UI occurring > 1 year after RARP.
PAK1-deficient mutant of C. elegans lives 60% longer than the wild-type. Interestingly, PAK1-deficient mutant of melanocytes produces less melanin (only a half compared with the wild-type) in the presence of either serum (PDGF) or α-MSH (alpha-melanocyte stimulating hormone). These observations indicate that the major "pathogenic" kinase PAK1 is responsible for both shortening the healthy lifespan, and PDGF/α-MSH-dependent melanogenesis. For screening of PAK1-blocking probiotic bacteria or their products, their anti-melanogenic as well as longevity promoting properties were examined. Recently it was found that C. elegans fed with Lactobacillus rhamnosus in Xinjiang cheese lives 40% longer than the worm fed with the standard E. coli. Interestingly, a Chinese traditional medicine called "ChiBai" fermented with the Lactobacillus rhamnosus also inhibited the α-MSH-induced melanogenesis, and this bacteria itself produces butyric acid that blocks the oncogenic HDAC (histone deacetylase)-PAK1 signaling pathway. These findings strongly suggest, if not proven, that anti-melanogenic activity of Lactobacillus and many other probiotic bacteria might serve as a reliable indicator for their longevity promoting activity. In this context, a popular Japanese Lactobacillus-fermented milk drink called "Calpis", developed a century ago, and recently proven to inhibit the melanogenesis by suppressing the PAK1-dependent tyrosinase gene expression, may potentially prolong our healthy lifespan.
Corticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. No benefit in patients not requiring respiratory support at randomization was observed. However, we believe that the use of corticosteroids in patients with COVID-19 pneumonia might not be subject to a decision based solely on oxygen needs. Evidence has shown that 30% of COVID-19 patients in its initial phases will progress to acute respiratory distress syndrome, particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that corticosteroids in patients with COVID-19 in its initial phases and risk of progressing to severe disease might lead to a decrease in the development of acute respiratory distress syndrome, and thereby reduce death.
Arsenic has widespread use in agriculture, in alternative medicine and in treatment of certain malignancies, therefore it is vital to timely recognize and treat arsenic toxicity in a suspected patient. Hemodialysis conventionally is thought to play only a supportive role in managing arsenic toxicity but it can be life-saving when chelation is not possible or available. A middle-aged female with a history of non-dialysis-dependent chronic kidney disease (CKD) was brought to the emergency with altered sensorium. On presentation, she was hemodynamically stable with pallor and exfoliating lesions on palms, hyperkeratotic lesions on soles and hyperpigmented macules on the trunk. Investigations revealed pancytopenia and deranged kidney function tests. In view of skin lesions, the toxicological analysis was sent which revealed high levels of Arsenic (594 and 2,553 mcg/L in blood and urine respectively). Thus, a diagnosis of metabolic encephalopathy with the underlying cause being uremic or/and arsenic intoxication was made. Considering renal failure, she was managed with thrice-weekly hemodialysis. Chelation was not possible due to unavailability of agents during lockdown in Coronavirus disease (COVID-19) pandemic. Following dialysis, there was a significant improvement in sensorium, skin lesions, and pancytopenia depicting the utility of hemodialysis in such cases. Thus, hemodialysis is an effective and perhaps underutilized modality in the treatment of arsenic intoxication with impaired renal function.